71. Bench to Bedside: ADHD stimulants do NOT impact the brain's attention networks?!?! with Dr. Nico Dosenbach

Bench to Bedside: How ADHD Stimulants Really Work—Arousal and Reward, Not Attention Networks

Dr. Elise Fallucco launches a new “Bench to Bedside” series and interviews Dr. Nico Dosenbach, senior author of a ground-breaking fMRI study published in CELL  that found that  stimulants do NOT significantly change the brain’s attention networks!?!?! 

Instead, effects are strongest in arousal (less drowsy, more wide awake) and reward/motivation systems (increasing predicted reward and tolerance of “drudgery”). 

We discuss:

• how these findings align with patient experience
• why ADHD can be a misnomer 
• how video games/TikTok exploit variable reward schedules
• how this changes what we tell patients and families about stimulants

Our conversation highlights implications for destigmatizing ADHD, reframing stimulants as helping wakefulness and motivation rather than “making you smarter,” and how strategies like habit pairing and gamification can make necessary tasks more rewarding.

00:00 Welcome to Bench to Bedside Series

01:34 What We Thought We Knew about Stimulants

03:30 Examining brain networks in ADHD

04:03 No Attention Network Effect

04:50 Patient reaction to the paper's fundings

05:30 Where in the brain are stimulants working?

05:45 Arousal Signature

06:29 Stimulants also affect the Dopaminergic REWARD and Motivational systems

06:41 "More Tolerant of Drudgery"

07:18 Stimulants affect Arousal

08:08 Stimulants act on Motivation and Reward

08:50 Why motivation matters in kids with ADHD

09:21 Findings consistent with other human behavioral data and macaque data

09:47 Raking Leaves and Hacking the Reward Systems

11:24 Clinical Implications of Study

11:41 Implications for ADHD Treatment

12:58 Did Einstein need stimulants?

13:16 Hyperfocus and Real Life Examples: Deer Hunting

15:24 Reward Hacking : Video Games and TikTok

16:42 Non Prescription Tricks to Hack the Reward System

18:15 Procrastination in ADHD and dopamine

19:01 Different ADHD distribution in medicine?

19:34 Reframing ADHD

20:26 Gamifying Life

22:09 Closing Recap - Clinical Implications

About Our Guest, Dr. Nico Dosenbach:

https://dosenbachlab.wustl.edu/

For access to the full paper, Stimulant medication affect arousal and reward, not attention networks:

https://www.cell.com/cell/fulltext/S0092-8674(25)01373-X

Check out our website PsychEd4Peds.com for more resources!
Follow us on Instagram @psyched4peds

Transcript

Dr. Elise Fallucco 0:21

Welcome back to Child Mental Health for Pediatric Clinicians. I'm your host, Dr. Elise Fallucco, child psychiatrist, and mom. Today is the start of a new series on the pod called Bench to Bedside, where we discuss the latest science in child mental health that has the potential to change your practice. And for this, we have on our podcast, the senior author of the groundbreaking study recently published in the journal Cell that has overturned our understanding of how stimulants work in the brain. Without giving too much away. In our discussion, we're gonna talk about how he and his team found out that A DHD stimulants do not impact the brain's attention networks. He's gonna tell us how stimulants actually work in the brain, and we are gonna talk about other things like how A DHD is a misnomer and some of the strengths of children and adults with A DHD. We're gonna talk about video games and TikTok and hacking into a variable reward schedule, and even about the biological basis of procrastination. But first a little bit about our guest. Dr. Nico Dosenbach is the David m and Tracy s Holtzman professor of neurology at Washington University in St. Louis. He's a pediatric neurologist and he also holds faculty appointments in the departments of pediatric radiology, psychological and brain sciences, and biomedical engineering. So please join me in welcoming to the pod, Dr. Nico Dosenbach.

Dr. Nico Dosenbach 1:52

Thank you. Thanks for having me.

Dr. Elise Fallucco 1:53

Thanks for being here. So let's get into it. I'm excited to talk about your study, but I wanna start with a little bit of background. For years we've been telling our patients with A DHD that stimulant meds improve your ability to pay attention. To concentrate and focus. Prior to conducting this recent study on the effects of stimulants on the brain, what have we really known in the field about how stimulants work and where they work in the brain?

Dr. Nico Dosenbach 2:22

That's a good question. Um, I mean, I think the, the sort of the story in both the research literature and I think what, you know, what I learned in residency or what I would tell my patients. Was exactly what you said that, these drugs help, in A DHD because they improve the ability to pay attention. Research is difficult and the kind of research that was probably backing this the most, which is human functional, MRI or FMRI research, it's still growing up and getting better every year. The very earlier studies, weren't of the highest quality. but we've been doing this for a long time. The functional MRI research, and I would say in the last, five years or so, the methods have gotten better again. And we have access to better and more data. like we have a, we are looking at the brain, but now we have a better microscope. So it's really easy to see more detail.

Dr. Elise Fallucco 3:11

To recap some of the things you said. Yeah. Academically what we've been taught or what was like, the academic dogma is that stimulants work by improving your attention. And so presumably by having some sort of effect on the attention networks of the brain.

Dr. Nico Dosenbach 3:24

Yeah.

Dr. Elise Fallucco 3:24

And so what your study did, I love the analogy you used, you said it's like our study used a better microscope, looking at functional MRI in a very large sample of nearly 6,000 children some of whom were taking stimulants to really ask the question and determine the answer, what is it that stimulants are doing in the brain, and can you share with us the major findings from your study?

Dr. Nico Dosenbach 3:50

Yeah, absolutely. So what we were looking for, what we thought we would find was. Changes in the brain's attention networks, and that there would be changes in those networks related to taking a stimulant. And we had two data sets. We had a large. Population sample of children called the EBCD Adolescent Brain Cognitive Development Study. And then we also had a clinical trial that was a small sample size clinical trial of adults. Taking stimulant and scanning them prior on the medication and then afterwards off. Which is a totally different approach. The results were significant. They showed the same result from both approaches, and the result was that there's absolutely no change in the brain's attention networks. Actually, if you take all the brain regions and rank order them. By how much are they affected by stimulants? The main attention network came in dead last,

Dr. Elise Fallucco 4:38

even the title of your article called out this, very unexpected finding. It's, the title of the article is Stimulant Medications Affect arousal and Reward Not Attention Networks. And that is somewhat earth shattering in our field because literally we call these Attention Deficit Hyperactivity Disorder meds. Yeah. And your study in your group is saying there's actually. No effect, no significant effect in the attention networks in the brain among people who are taking stimulants.

Dr. Nico Dosenbach 5:11

It's actually funny story, once the paper came out, lot of patients on stimulant medications they were all saying. Who, whoever thought that A DHD meds improve your attention? That's not what it feels like to me. Don't discount the patients. Like they, they know. It's almost like 99% of patient responses that read the article. The abstract were just like yeah, duh. Like why is this a cell paper?

Dr. Elise Fallucco 5:37

Patients themselves have a different lived experience as you're describing They take stimulants, they understand how the stimulants work and they experience it not even as much as if this is improving my attention, but in a different way.

Dr. Nico Dosenbach 5:50

Yeah, that's right.

Dr. Elise Fallucco 5:51

So we know that stimulants ultimately have positive effects. On performance in children and adults with A DHD. So now here is where you tell us more about exactly where in the brain did you find that stimulants were working? I.

Dr. Nico Dosenbach 6:06

There were very strong reproducible effects and they were. Related to, I would call an arousal signature. So there's essentially a signature of being. Less drowsy or wide awake, which of course fits with, stimulants. The results meant that instead of making you better at attention, it looks like. You're wide awake. Which half of kids in America are sleep deprived, that's in that data set too. and if you're sleep deprived, taking a stimulant will partially offset that. And so you'll have better performance and you'll feel better.

Dr. Elise Fallucco 6:38

So one of the findings that you, your study team had is that the big difference that the stimulants are making in the brain is in the networks and brain regions associated with arousal with being awake and alert. Yes.

Dr. Nico Dosenbach 6:50

Yes. And then the other signature was related to dopaminergic. reward or, sort of prediction error learning systems, but essentially motivational systems, right? And the imagery I like is it makes you more tolerant of drudgery of things you don't like doing. Because the perceived predicted reward is higher the wild card here is that what some one person considers drudgery is another person's hobby and vice versa. There can be some idiosyncrasies, but essentially if you don't want to do it, which you know, for a lot of kids would maybe be math homework, it can essentially pre reward you raise your floor on the dopamine because you need dopamine to do anything, right? If you don't have enough predicted reward from an activity you're just not gonna do it, especially as a kid.

Dr. Elise Fallucco 7:39

So I wanna stop you there so you talked about the two ways that stimulants act in the brain And the first is in the arousal system, making you feel wide awake. you also highlighted that there's such a big problem with sleep deprivation and that the stimulants, as you found in the study, can. Essentially reverse that.

Dr. Nico Dosenbach 7:58

Yeah they stimulus seem to reverse the brain signature of drowsiness and the cognitive deficits, which I'm not sure you should call it deficit.'cause it's temporary. It's everybody knows, especially any physician, if you haven't slept, you're not at your best. What's interesting there is it's completely unknown whether or not that's a true effect in the sense that it can truly biologically recover the physiological essence of having slept of it, just papers over it. And there's a price to pay later, either right that evening or maybe like years down the road.

Dr. Elise Fallucco 8:29

This gets to the second area of the brain that stimulants are working in according to your study. The stimulants are acting on the motivational systems or the drive as you put it. And I like basically able to override this sense of, this is boring and I don't wanna do it. And it pre rewards people kind of. Raises the floor on dopamine and increases their drive and motivation to complete a task that previously would've been really boring. And that in turn may be the mechanism for better performance at school, better performance at cognitive tests, because you don't. Get bored or annoyed and drop out or, decide to do something more exciting. And that's why this issue of reward and motivation is so key.'cause we know with A DHD that when you do have a lot of motivation and you're just inherently interested in it, that you can lock in and focus. And the issue is it's harder to pay attention with things that you consider to be boring or drudgery. And unfortunately. Sometimes those things may occur during school hours or in certain classes, and that makes it really hard for kids to be as successful in school and to just enjoy school.

Dr. Nico Dosenbach 9:43

But it fits with a lot of other behavioral data in humans. Even in, in macaques, for example, that. stimulants don't make you smarter, which of course it'd be like, how would that even work, right? It's just that when you don't want to do something or you're tired of both, you're not gonna do very well at it. And if you're now wide awake and you're gonna persist longer'cause it feels less boring, you're gonna have better performance. But you're no smarter. And, and finishing this paper, I tried my own version of this. I made a mistake. I bought this house that has a giant yard with all these trees. So now I'm like a tree farmer. And in the fall it's just covered in leaves, and I'm old and I'm there with my rake and I got three kids, the youngest two young, but the older two are 10 and 13 they could rake. So I tried and said, Hey. Help your old man rake these leaves before I have a back spasm. And they both look at me and they go

Dr. Elise Fallucco 10:34

no. This is boring. Yeah, why would I do that, dad?

Dr. Nico Dosenbach 10:37

And they're, they're physically active, they're like running around. They do, but they don't wanna rake. So I said, okay, I'll pay you. Which already I feel weird about, but I really didn't wanna, get a back spasm, go to the er. So And they're like, no. And then I rake a pile, not a very big one, and the youngest one just jumped in it. And then you can see the older two, they look at me and I'm like, you can't jump in that you're gonna hurt yourself, like you're much bigger. And then my daughter goes, what if we rake a really big pile? Would it be safe to jump in it? It's if it's enormous, if we take all the leaves in the yard and make one giant pile. You get to jump in it. Then they both ran in the garage, got the extra rakes and started raking. And I felt like a trickster.'cause I was like, oh my God, now they're raking, right? But it's like the same activity. But now they've changed how they think about it. And the predicted reward is no longer, my dad won't yell at me for being lazy. It's like I get to do this fun thing, jump into a giant pile of leaves and it worked. Yes. And it did great for a long time and then they started jumping the leaves and I was, I was like, this is hilarious.'Cause it's the same thing, but it depends on how you see it.

Dr. Elise Fallucco 11:45

Exactly. Which brings us to this question of what are the clinical implications of these findings? how does this change how we approach either treatment for A DHD and or how we talk to families about how stimulants work?

Dr. Nico Dosenbach 12:00

Great question. would say one thing, I think we got grilled on a lot was there's definitely some folks who are antis stimulant medications. You could probably explain to me why exactly.'cause sometimes I'm like, why are you even, and so they, they, they would be fishing for like, okay, so you found a different explanation for how they works. So they, they don't work. And I'm like, no, that's not what that means. They work, like there's clear evidence in the data that kids with a DHD on stimulants do better at school and a better on cognitive tests, for example. I think on the medications side, the medications work I think it's the mindset surrounding it, right? Feel like it can't hurt to understand better what's going on and what you're struggling with and how the medicine helps you. It's compensating for this deficit. Or, I'm not even sure it's a deficit'cause the protective mechanism against spending too much time in drudgery. Are stronger than some than others. But if you're gonna school and you don't like math and you have to do homework then you need help. And it's fine. It's not cheating. It's not like an unfair advantage.

Dr. Elise Fallucco 12:58

yeah. It's not, it doesn't make you smarter. It just helps you be more awake and more motivated to do things. Yeah. That you wouldn't. Particularly be interested in,

Dr. Nico Dosenbach 13:07

and you don't need it for your favorite thing. I'm probably sure you could go down to the line and ask people with a DHD, what's your favorite thing? And then go, do you need a stimulant to do that? And they'll all say no. And that could be video games or hunting or racing dirt bikes. Like Albert Einstein, probably, even if he had a DHD, wouldn't need have needed stimulants because the thing he spent all his time on, he found fascinating naturally, and he, if he didn't need help with that, it probably would've helped him, I don't know, get more haircuts more frequently or, do stuff he didn't like with taxes. I mean, I always felt that this, the A DH ADHD was sort of a weird terminology given that people with that diagnosis often hyperfocused. One example I used before is, you know, for my practice, I remember this one kid, I'm here in Missouri, and out in the country people go hunting. And so this dad comes in with a kid. And he goes, I think he's faking a HD at school. And I go, okay, why is that Tommy? He's like, well, I took him hunting at this season, and he sat in a high stand without moving a muscle for many hours. He actually wanted to keep going when I was like, I'm cold. I want to go home. And then supposedly at school, he can't sit skill, especially in math, right? And I was always like, what? What is that? And so with this view now that I have, based on the study, it's like, well, apparently he loves hunting.

Dr. Elise Fallucco 14:23

Yeah,

Dr. Nico Dosenbach 14:23

he does not like math.

Dr. Elise Fallucco 14:24

Yeah.

Dr. Nico Dosenbach 14:24

And so the predicted reward of seeing a deer and shooting it, which isn't everybody's thing, but he seems to like it keeps him in his in a spot and doing the thing. You know, I'm sure every clinician's heard those stories before, like, you know, like the kid who can't even stay in the classroom, but it is like an ace dirt bike racer or something, you know, which requires the super focus so you don't crash.

Dr. Elise Fallucco 14:45

Clinically, what I've seen is, um, parents think that A DHD is just such a misnomer, and they'll say, you know, thank you very much Dr. Fallucco, but I don't think my child has a DHD because you should see him play video games. He can really lock in for hours. Yeah. You know, and. Um, can persist with multiple distractions and still wanna go after the next level and the next level. Yeah. And you know, that's why this issue of reward and motivation is so key.'cause we know with, with A DHD that when you do have a lot of motivation and you're just inherently interested in it, whether it's deer hunting or Roblox, that you can lock in and focus. And the issue is it's harder to pay attention with things that you consider to be boring or drudgery. And unfortunately. Sometimes those things may occur during school hours or in certain classes, and that makes it really hard for kids to be as successful in school and to, frankly to just enjoy school. So, um,

Dr. Nico Dosenbach 15:45

yeah, and I mean, video games are probably the one that comes up the most, I feel like, but it's a sort of globally trillion dollar industry that is designed to hack into a young person's reward system. Right? I mean, they're explicitly designed with a variable reward schedule. To, to, to, to be rewarding, right? I mean, that's, that's the, that's how they make money. And so it's not that surprising that, you know, there's sort the one thing where often people will say, you know, like, yeah, my kid can play video games all day, but not do homework. No, no. Duh. Right? I mean, this, this,

Dr. Elise Fallucco 16:19

it has

Dr. Nico Dosenbach 16:19

nobody designed homework to be addictive and super fascinating.

Dr. Elise Fallucco 16:24

But maybe they should. Oh my gosh. How, how cool would that be?

Dr. Nico Dosenbach 16:28

Yeah.

Dr. Elise Fallucco 16:29

And,

Dr. Nico Dosenbach 16:29

and I think other things, sorry, like scrolling reels, right? Like TikTok and stuff. all these companies hired a bunch of academic psychologists who study the reward system and all of their algorithms reflect their understanding of how that works in the brain.

Dr. Elise Fallucco 16:42

Exactly. The video game manufacturers and the social media brilliant geniuses know how to hack into the reward system, and they do it very effectively and get people drawn in and persisting for insane amounts of time. Um, but we don't have that same technology applied to elementary, middle, and high school education, um, necessarily.

Dr. Nico Dosenbach 17:03

A lot of people have like non-prescription tricks that are similar to stimulants to get themselves to do things. Like you start talking to people, they're like before I do unpleasant task X, like before I do the laundry, I always have to have a piece of chocolate. It's not as strong, but there's like a mild dopaminergic effect. Or I eat some gum bears or or I go for a run You're doing the same thing, except mine's less healthy, it's chocolate, and yours is, you go for a three mile round and then you're like, now I can do my taxes.

Dr. Elise Fallucco 17:30

So like non-prescription tricks to treat a DHD it makes me think of this book, atomic Habits where they talk about exactly what you were describing, which is habit pairing, Pairing something that you don't particularly like to do with something that is rewarding and fun like chocolate or running or whatever it is, depending upon Yeah. You individually that when you associate those two things with one another, then it gets you to do the thing you don't wanna do. And it's, which is exactly what we're saying stimulants are doing, by pre rewarding you increasing your motivation and your drive to do something. Yeah. And it makes me think. That we need to think more broadly for all of our kids with A DHD and family members with A DHD to try to figure out, what is the most challenging thing for you to do during the day that is also important for functioning well and then how can we zero in on that, either in therapy or in discussion with the families to figure out a way to somehow habit pair or make that more rewarding naturally.

Dr. Nico Dosenbach 18:27

absolutely. I used to see this in myself and some people in my family. For example, this procrastination thing where I was like, okay, I can't do X yet. Say taxes. It's coming up April 15th. Almost nobody likes taxes. And so it's oh, I'm procrastinating because it's no, I'm gonna do this fun thing, and then later in the day I'm gonna do my taxes. I used to beat myself up about that kind of behavior morally.'cause it's like, why are you procrastinated? It's bad. Now I realize no, it's like my brain is like you woke up and there's no predicted reward and your dopamine's low. But if you, I don't know, go to the pool with the kids, then you can do your taxes. Like you're not bad. once you can understand it, you don't need to beat yourself up. Be mystified as much by your own behavior or by your kids as or by your relatives or whatever, right?

Dr. Elise Fallucco 19:11

I mean it's how we're entirely wired. Like we're driven towards things that are rewarding and we've been designed or wired in a way that the things that we need to do for survival, tend to be more rewarding.

Dr. Nico Dosenbach 19:22

Medicine, for example. A few years ago I started noticing that the different Medicine, subspecialties had like different A DHD distributions.

Dr. Elise Fallucco 19:29

Yes.

Dr. Nico Dosenbach 19:30

Like the E, the ER and ICU have much higher percentages and it totally makes sense'cause you need this excitement and moving from spot to spot. But it also makes you much more tolerant of what other people consider stress. And then there's some subspecialty like peds id. Every patient is a four hour visit and the history is 20 pages long. I mean like a lot. And there's not that much of sudden excitement and beeping. I haven't yet to meet someone in that specialty that has a DHD.

Dr. Elise Fallucco 19:55

yeah. But you bring up a really good point here, which is. one of the things that we can do as adults is to try to help de-stigmatize having a DHD reframing It as, it's not that you have any cognitive deficits or there's anything wrong with the way you think or how smart you are. I love how you put it. You said It's just your brain. Has a really big protective effect against drudgery and boredom. Your brain does not really like to be super bored. Not, and that's not a bad thing. But if you're coming to me because you're failing school or having major problems, okay. We've gotta get over that obstacle somehow so that we can get you on the path of doing the thing that you love and being successful. So these stimulants meds will increase your motivation and drive to do the kind of boring things at school, like whatever they are. And will keep you awake and paying attention so that you can get back to doing the things that you love.

Dr. Nico Dosenbach 20:47

My entire life, I've gamified things I didn't like on purpose. To make them more bearable. Nowadays, if you work at university, you have a lot of online trainings that are common sense and you have to do the same one every year.

Dr. Elise Fallucco 21:00

The hurricane preparedness for Florida, like every year I have to answer questions about how many gallons per person, per day of water do you need during hurricane season? Anyway, go on.

Dr. Nico Dosenbach 21:10

The only way I can do it now is. I remember my time from last year and I essentially try to do it really fast. I was like, I bet I can do this in nine minutes, because otherwise I don't even wanna do it at all. But now I'm like, oh look, I beat my time from last year. I did it in under nine minutes. But now it's like in at work or something if, it's like really nobody wants to do it. You like make it a game. You know what I mean?

Dr. Elise Fallucco 21:33

yeah.

Dr. Nico Dosenbach 21:34

You can do it the fastest or the most, or who can get the high score?

Dr. Elise Fallucco 21:38

as parents, as therapists, as psychiatrists, as family members, whoever, maybe part of our job is to try to help figure out ways to make things more rewarding. Yeah. Make things more fun and even gamify them. Yeah. And this works for everybody. Like I, I'm an adult who needs to do a lot of things that I don't wanna do. Yeah. Increasing my pre reward. If that gets things done faster that's not a bad thing. And then like maybe take some cues or pages from the playbook of the video game manufacturers and the social media gurus. Use the same reward system. I am so glad that I had this opportunity to talk with you, and it is such a treat for our listeners and for me to be able to learn about these incredible findings and to be part of the science of moving, our understanding of stimulant medications forward. So thank you for your contributions and for joining us on the podcast.

Dr. Nico Dosenbach 22:29

Thanks for inviting me.

Dr. Elise Fallucco 22:31

And now for our listeners, I just wanna recap high points and mainly talk about the clinical implications of this really groundbreaking study. And I wanna borrow from one of the analogies that Dr. Dosenbach used. Now that we have a more powerful microscope, metaphorically, to look at the brain, we have a better understanding of how stimulants work in the brain. And with this better understanding, it can help us explain to patients and families how stimulants work. So while this study showed that stimulants do not work in the attention networks in the brain, we know that they're working in other parts and in other areas to improve performance and behavior. put simply stimulants work in the brain by helping us to feel more wide awake, AKA increasing arousal, and also by increasing dopamine and tapping into our motivational systems to give us more drive, to increase our experience of Predicted reward. Or to help make things that previously would've been boring. Seem like they're more fun, and that in turn helps us become more engaged and helps us be able to lock in and do what we need to do to be at our best. So while the stimulants are not directly working on the attention networks of the brain, we now know that they're helping us feel more awake and more motivated, which in turn translates into improved performance. And oftentimes improve behavior because you're not feeling as bored. And I just wanna thank you all for joining us on this new Bench to bedside type episode and series of the pod If you enjoyed this, I really hope you'll share it with a friend or colleague. And as always, feel free to click our link in the show notes to our website. Psyched the number four peds.com to join our newsletter or to send in any questions or ideas you have for future episodes. Thanks so much for tuning in. Look forward to talking to you next time.